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Stem cell transplantation

Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma


Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3–4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.

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Fig. 1: Survival outcomes after alloHCT.
Fig. 2: Survival outcomes based on donor type and GVHD prophylaxis regimen.
Fig. 3


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RWM acknowledges support from an ASH Research Training Award for Fellows, the ASH Clinical Research Training Institute, an ASBMT New Investigator Award, and the LRF Lymphoma Clinical Research Mentoring Program. This research was supported in part by National Institutes of Health award number P01 CA23766 and National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported in part by a grant from the Italian Association for Cancer Research (AIRC, grant #20575 to CC-S).

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Authors and Affiliations



RWM designed the research, collected and analyzed data, and wrote the paper. LC, LG, CdP, PA, PLZ, and CC-S designed the research, collected and analyzed data, and edited the paper. VTH, PC, AG, BC, DAB, SJ, MAS, SA, RL, GLS, M-AP, JMSdC, DB, AFH, GS, CS, SMA, YN, TB, MH, TAF, LD, AKS, JPM, TN, JC, AVS, JK, MM, RD, AS, RH, GM, M-PM-M, CO, KB, DM, RR, LL, AB, MJF, Y-BC, RCL, SDS, UR, MTB, JTR, JBC, SN, TP, RMJ, MR, AB, HJB, JS, VT, MS, MM, and AS collected data and edited the paper.

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Correspondence to Reid W. Merryman.

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Conflict of interest

RWM, LC, LG, VTH, PC, AG, BC, MAS, SA, RL, JMSdC, DB, LD, AKS, TB, GS, CS, SMA, AVS, M-PM-M, CO, KB, LL, A Beitinjaneh, UR, MM, RD, SN, TP, RMJ, MR, A Bashey, HJB, JTR, VT, MS, CdP, and MM—none. DAB—Honoraria: Seattle Genetics. SJ—Honoraria: Novartis, Kite, Juno, Takeda, CRISPR Therapeutics. GLS—Research funding: Janssen, Amgen. M-AP—honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Kite/Gilead, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda. He serves on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune. He has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec. He serves in a volunteer capacity as a member of the Board of Directors of Be The Match (National Marrow Donor Program, NMDP), as well as on the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Executive Committee. AFH—Research funding: BMS, Merck, Genentech, Inc./F. Hoffmann-La Roche Ltd., Gilead Sciences, Seattle Genetics, Immune Design, AstraZeneca, Pharmacyclics. Consultancy: BMS, Merck, Genentech, Inc./F. Hoffmann-La Roche Ltd., Gilead Sciences, Seattle Genetics, Karyopharm. Travel, Accommodation, Expenses: BMS. YN—Consultant: Affimed. Research funds: Astra Zeneca, Affimed, Novartis, Secura Bio. MH—Research Support/Funding: Takeda Pharmaceutical Company; Astellas Pharma. Consultancy: Incyte Corporation; ADC Therapeutics; Celgene Corporation; Pharmacyclics, Magenta Therapeutics, Omeros, AbGenomics, Verastem, TeneoBio. Speaker’s Bureau: Sanofi Genzyme, AstraZeneca. TAF—Consultant./Ad Board: Seattle Genetics/BMS/Celgene/Karyopharm/KITE. Honoraria: Takeda/Celgene/Seattle Genetics/AbbVie/Pharmacyclics/Janssen/KITE/BMS. Speaker Bureau: Takeda/Celgene/Seattle Genetics/AbbVie/Pharmacyclics/Janssen/KITE/BMS. JPM—Research funding from Novartis, Fresenius Biotech, Astellas, Bellicum Pharmaceuticals, Gamida Cell, Kite Pharmaceuticals, Pluristem Ltd., Juno Therapeutics, and AlloVir. Advisory board and travel accommodations/expenses from Kite Pharmaceuticals, Juno Therapeutics AlloVir. Honoraria from Kite Pharmaceuticals and AlloVir. TN—Research funding: Novartis and Karypharm. JC—Personal fees: Kite/Gilead, Novartis, Morphosys, Bayer, Epyzime, AstraZeneca, Genentech, Karyopharm, Celgene/Juno. Research Support: Merck. JK—Research funding: Merck. AS—Honoraria: Celgene. Consultancy: Takeda. Other: Pfizer. RH—Honoraria: BMS, MSD, Gilead, Kite, Roche, Novartis, Janssen, and Celgene. GM—Honoraria: Bristol Myers Squibb. DM—Editorial board: MorphoSys. RR—Research funding: Merck. Consultancy/Advisory: BMS. MJF—Consultancy/Advisory board: Novartis, Kite/Gilead, Celgene/BMS, and Arcellx. Y-BC—Consulting: Magenta, Incyte, Abbvie, Daiichi, Equilium, Actinium, Takeda. RCL—Research funding: Juno Therapeutics, Takeda, TG Therapeutics, Incyte, Rhizen Pharmaceuticals, Bayer, Cyteir, Genentech. Consultancy: MorphoSys. SDS—Research funding: Acerta Pharma BV, Astrazeneca, Bayer, Beigene, Ayala, Bristol Myers Squibb, De Novo Biopharma, Genentech, Ignyta, Incyte Corporation, Merck, Sharp and Dohme Corp., Pharmacyclics, Portola Pharmaceuticals, Seattle Genetics. Consultancy or Advisory Board: Astrazeneca, Millenium/Takeda, Beigene, Karyopharm, KITE pharma. MTB—Research funding: Karyopahrm. Consulting: Concert, Celgene/Celularity. JBC—Research funding: BMS/Celgene. JS—Consultancy: Adaptive, AstraZeneca, Atara, BMS, Genmab, Imbrium, Pharmacyclics, and Seattle Genetics. Research Funding: AstraZeneca, BMS, Incyte, Merck, Pharmacyclics, Seattle Genetics, and TG. AS—Advisory Board: BMS, Servier, Gilead, Pfizer, Eisai, Bayer, MSD. Consultancy: Arqule, Sanofi. Speaker’s Bureau: Takeda, BMS, Roche, Abbvie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD. PA—Consultancy: Merck, BMS, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome. Research funding (inst): Merck, BMS, Affimed, Adaptive, Roche, Tensha, Otsuka, Sigma Tau, Genentech, IGM, Kite. Honoraria: Merck, BMS. PLZ—Consultancy: Verastem, MSD, Eusapharma, Sanofi. Speaker’s Bureau: Verastem, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, MSD, Immune Design, Celgene, Portola, Roche, Eusapharma, Kyowa Kirin. Advisory Board: Verastem, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, MSD, Immune Design, Celgene, Portola, Roche, Eusapharma, Kyowa Kirin, Sanofi. CC-S—Consultancy: Servier, ADC Therapeutics, Roche, Sanofi, BMS, Merck, Karyopharm. Honoraria: Janssen Oncology AstraZeneca. Research support: ADC Therapeutics, Rhizen Pharmaceuticals.

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Merryman, R.W., Castagna, L., Giordano, L. et al. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma. Leukemia 35, 2672–2683 (2021).

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